Copyright ©The Author(s) 2016. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Psychiatr. Mar 22, 2016; 6(1): 54-65
Published online Mar 22, 2016. doi: 10.5498/wjp.v6.i1.54
Sex differences in cognitive impairment in Alzheimer’s disease
Keith R Laws, Karen Irvine, Tim M Gale
Keith R Laws, Karen Irvine, Tim M Gale, School of Life and Medical Sciences, University of Hertfordshire, Hatfield, Hertfordshire AL10 9AB, United Kingdom
Karen Irvine, Tim M Gale, Hertfordshire Partnership University NHS Foundation Trust, the Colonnades, Beaconsfield Close, Hatfield, AL10 8YE, United Kingdom
Author contributions: All authors contributed to this paper and approved the final manuscript.
Conflict-of-interest statement: The authors have no conflicts of interest to declare.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
Correspondence to: Keith R Laws, PhD (CANTAB), Professor, School of Life and Medical Sciences, University of Hertfordshire, College Lane, Hatfield, Hertfordshire AL10 9AB, United Kingdom.
Telephone: +44-1707-281137
Received: August 20, 2015
Peer-review started: August 22, 2015
First decision: October 30, 2015
Revised: December 21, 2015
Accepted: January 21, 2016
Article in press: January 22, 2016
Published online: March 22, 2016

Sex differences in neurocognitive abilities have been extensively explored both in the healthy population and in many disorders. Until recently, however, little work has examined such differences in people with Alzheimer’s disease (AD). This is despite clear evidence that AD is more prevalent in women, and converging lines of evidence from brain imaging, post-mortem analyses, hormone therapy and genetics suggesting that AD affects men and women differently. We provide an overview of evidence attesting to the poorer cognitive profiles in women than in men at the same stage of AD. Indeed, men significantly outperform women in several cognitive domains, including: Language and semantic abilities, visuospatial abilities and episodic memory. These differences do not appear to be attributable to any differences in age, education, or dementia severity. Reasons posited for this female disadvantage include a reduction of estrogen in postmenopausal women, greater cognitive reserve in men, and the influence of the apolipoprotein E ε4 allele. Assessment of cognitive abilities contributes to the diagnosis of the condition and thus, it is crucial to identify the role of sex differences if potentially more accurate diagnoses and treatments are to emerge.

Keywords: Dementia, Gender, Sex differences, Cognition

Core tip: This review assesses evidence that women with Alzheimer’s disease (AD) show greater cognitive impairment than men. The evidence shows that female AD patients are outperformed by males in multiple cognitive domains including visuospatial, verbal processing, semantic and episodic memory. This disadvantage is not attributable to sex differences in age, education level, or dementia severity. Possible explanations include estrogen loss in women or a greater cognitive reserve in men, which may provide protection against the disease process. Such findings have implications for tailoring more specific gender-based treatments.